The objectives of this study are to ascertain biological, physiological and clinical mechanisms of male reproductive disorders and to provide rational strategies of treatment for men with reproductive disease. This project represents a continuum of research begun in 1970 and includes studies of 1) the hormonal regulation of spermatogenesis in gonadotropin deficient men, 2) biology of sperm function 3) adverse effects of cancer therapy on gonadal function 4) evaluation of treatment of men with reproductive disorders and 5) the role of sex steroids in regulation of gonadotropin secretion. Major findings from studies performed during the past year have shown 1) that stimulation of androgen production alone in men with partial panhypopituitarism or pituitary tumors may be sufficient to induce fertility 2) that enyme deficiency within sperm correlates highly with deficient motility of sperm from infertile men 3) that the sperm of some infertile men show absence of specific epididymal proteins required for sperm-egg fusion 4) that cerebral glucose metabolism is altered in hypogonadal subjects 5) that sex steroids regulate gondotropin secretion from the pituitary primarily by modulation recruitment of new gonadotropes 6) that GnRH modultes glycosylation of LH subunits and 7) that prolactin secretion is markedly enhanced and parallels the high FSH levels induced by decreased androgen and increased estrogen.